11-33886409-T-G

Variant names:

• chr11-33886409-T-G
• rs4756077
• NM_005574.4:c.-335-4522A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005574.4(LMO2):​c.-335-4522A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,024 control chromosomes in the GnomAD database, including 44,556 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44556 hom., cov: 31)
• Consequence: LMO2 NM_005574.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 8 publications found

Genes affected

LMO2 (HGNC:6642): (LIM domain only 2) LMO2 encodes a cysteine-rich, two LIM-domain protein that is required for yolk sac erythropoiesis. The LMO2 protein has a central and crucial role in hematopoietic development and is highly conserved. The LMO2 transcription start site is located approximately 25 kb downstream from the 11p13 T-cell translocation cluster (11p13 ttc), where a number T-cell acute lymphoblastic leukemia-specific translocations occur. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Nov 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMO2	NM_005574.4	c.-335-4522A>C		intron_variant	Intron 1 of 5	ENST00000257818.3	NP_005565.2
LMO2	XM_047426944.1	c.-433-4133A>C		intron_variant	Intron 1 of 6		XP_047282900.1
LMO2	XM_017017733.2	c.-264-4522A>C		intron_variant	Intron 1 of 4		XP_016873222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMO2	ENST00000257818.3	c.-335-4522A>C		intron_variant	Intron 1 of 5	1	NM_005574.4	ENSP00000257818.2

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115679 AN: 151906 Hom.: 44509 Cov.: 31

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.725

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.762 AC: 115784 AN: 152024 Hom.: 44556 Cov.: 31 AF XY: 0.758 AC XY: 56283 AN XY: 74278

African (AFR) AF: 0.870 AC: 36101 AN: 41472

American (AMR) AF: 0.666 AC: 10181 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2475 AN: 3470

East Asian (EAS) AF: 0.671 AC: 3466 AN: 5164

South Asian (SAS) AF: 0.737 AC: 3552 AN: 4818

European-Finnish (FIN) AF: 0.753 AC: 7942 AN: 10548

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.730 AC: 49592 AN: 67960

Other (OTH) AF: 0.719 AC: 1512 AN: 2102

Alfa AF: 0.737 Hom.: 70498

Bravo AF: 0.760

Asia WGS AF: 0.675 AC: 2346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.86
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4756077; hg19: chr11-33907955;